ACE Inhibitors May Not Prevent Chemo-Related Cardiotoxicity

The angiotensin-converting enzyme (ACE) inhibitor enalapril, a common blood pressure medication, had no impact on cardiotoxicity biomarkers in patients with breast cancer or non-Hodgkin lymphoma who were being treated with high-dose anthracycline chemotherapy, researchers have found.

“We were not able to prevent what's called a myocardial injury, which is basically a blood test rise that can occur with the chemotherapy,” explained Dr. David Austin, consultant cardiologist at the academic cardiovascular unit in James Cook University Hospital, South Tees, Middlesbrough, United Kingdom. “It's quite a specific blood test. It's a very, very sensitive blood test. We were hoping to be able to prevent that from happening with the [use of] heart medication. But unfortunately, we found that that wasn't the case.

“There had been some previous research and studies on animals that suggested that [enalapril] may be a preventative treatment. But it looks from our results, at least the early results, that it's probably not going to be an effective therapy.”

Austin was the lead author of the study, which was presented at the American College of Cardiology’s Annual Scientific Session, that enrolled 111 patients at 13 sites across the United Kingdom. The average participant age was 57 and, 78% were women and 62% had breast cancer. Half of whom received enalapril while undergoing chemotherapy, according to a news release from the American College of Cardiology. Researchers monitored patients’ levels of troponin, a biomarker associated with heart damage.

By the study’s endpoint, 77.8% of patients who received enalapril and 83.3% of those who received standard of care experienced troponin T release, while 47% and 45% tested positive for troponin I.

Cancer treatments including chemotherapy, radiation, targeted therapies and immunotherapy can cause or worsen conditions such as high blood pressure, abnormal heart rhythms and heart failure, according to a report from the American Cancer Society.

Ausitin discussed the study and its findings, and he explained how long-term effects such as cardiotoxicity are a result of the success of chemotherapy in treating cancer.

READ MORE: Biomarkers May Help Predict Heart Risk in Childhood Cancer Survivors

CURE®: What is known about the cardiotoxic effects of chemotherapy, especially in long term survivorship?

Dr. David Austin: Historically, these particular drugs, the anthracyclines, have been associated with a condition called heart failure, which sounds bad. In the small number of cases of patients who do get that condition, it can affect the quality and length of patient survival, for sure. Now, as this particular topic is investigated in more detail — and I think I should sort of break off and possibly say this is a consequence of the success of therapies, so we're dealing with the late effects of what have been successful treatments — we're noting that patients are now receiving quite lower doses of the treatments, and the heart failure that used to occur, let's say back 20, 30 years ago, is happening less frequently. When really investigate it in the clinical trials, where we're looking in great detail, quite a lot of the studies where they got two- or three year follow-up, are showing that really, the cardiac effects are only affecting a very small amount of patients.

Now, that's an important thing still, but perhaps I want to for your readership, and for the people who will be interested in this particular issue, to just understand where this sits. We don't want to be sounding alarm bells. As such, we just want to be raising the awareness of the importance of cardiac effects of cancer and its late effects, and we want to investigate it further to improve the survivorship.

Given these findings, that ACE inhibitors are not preventative to cardiotoxic effects, what comes next, research-wise?

That's a good question. First of all, our study looked at things at a very early stage and I think we need to be following our study up for longer, so that maybe means over two, three, four years. So for us, that's what our focus will be. But putting it all together, we need to think about how we monitor patients, for example, and I think we're increasingly seeing guidelines coming forward that suggests certain patients who are at risk should be monitored for longer to make sure that nothing happens later down the line. And patients maybe who've had very high doses of anthracyclines, which can occur particularly in some groups of patients, maybe those patients should be monitored for longer.

And although we didn't find the ACE inhibitors were preventative, so it didn't prevent the cardiac injury from occurring, that's not to say that some of these medications might not be helpful in the future for patients where [there is] more concrete evidence of cardiac dysfunction — so that's the heart function are deteriorating — they may be helpful in those patients, it's just to say that maybe having them upfront is probably not going to be beneficial.

Are there certain patient populations that are more at risk for cardiac issues?

I touched on dose, and our trial looks at those patients receiving the highest contemporary doses, so those are over a certain dose. So there are certain conditions where very high doses tend to be used — [such as] sarcoma, we didn't look at that in our study, but that is an area where quite high doses of anthracyclines are used. And increasingly, [patients with] lymphoma where maybe the patient is a little bit older, possibly, or has other cardiac issues in the background, for example, evidence of coronary heart problems or pre-existing heart problems. Those are the sorts of patients where closer monitoring is really required.

Now, I would have said in our study, because we needed patients who were not already needing those medications, those patients were perhaps underrepresented in our study, and therefore, in real-world, more unselected situations it very much goes on a case-by-case basis where if patients have an underlying problem preceding the treatment, they perhaps need a little bit more follow up.

Is there anything else you would like our readership to know about this topic?

[Cardiac toxicity from cancer treatment] is a greater focus now. This was not really an issue in cardiology when I trained, I don't think we were even talking about this. So, I think this is an element of the success of current therapies creating a new issue for us to be aware of in the longer-term survivorship. So, I think we're on it and more research is happening. And really, this is a focus for cardiology and oncology over the coming years.

Transcript has been edited for clarity and conciseness.

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